Effects of administration of co-trimoxazole and folic acid on sperm quality and histological changes of testes in male rats

Background: Male infertility has been reported following long-term sulfasalazine, however, the precise effects of co-trimoxazole on sperm quality is controversial.
Objective: In this study, we evaluated the effects of co-trimoxazole and its co-administration with folic acid on sperm quality and histological changes of testes in male rats.
Materials and Methods: In this experimental study, 136 male Wistar rats were divided into 9 groups: I (control), II (vehicle) received saline, III: received folic acid (1 mg/kg /daily i.p., and IV- IX received co-trimoxazole (30, 60, and 120 mg/kg/daily; i.p.)+folic acid (1 mg/kg/daily; i.p.) for 14 or 28 days. Sperm samples were obtained from each group at the end of 14^th and 28^th days. Sperm numbers, motility, and viability were evaluated on a hemocytometer. Hematoxylin and Eosin stained testes were done for evaluation ofthe number of Leydig cells, vascularity, spermatids, spermatocytes, and means of seminiferous tubules diameter under light microscopy.
Results: Co-trimoxazole treatment for either 14 or 28 days caused a significant decrease in the percentage of sperm number, motility, and viability (p<0.001) compared to the control group. Also, high doses of co-trimoxazole caused a significant decrease in testes structural abnormalities means of seminiferous tubules diameter, spermatids, and spermatogonia) compared to the vehicle group (p<0.001). Folic acid co-administration with co-trimoxazole partially reversed the decrease in sperm quality and structural abnormalities of high doses of co-trimoxazole (60 and 120 mg/kg/daily) (p<0.001).
Conclusion: The data showed the adverse effects of co-trimoxazole on sperm quality and testes morphology which was protected partially by folic acid co-administration in rats. The underlying mechanism (s) needs further investigations.